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[通过免疫组织化学研究分析快速破坏性髋关节炎(RDC)关节组织中基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)的表达]

[Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues of rapidly destructive coxarthropathy (RDC), analyzed by immunohistochemical study].

作者信息

Matsumoto F, Uzuki M, Kaneko C, Rikimaru A, Kokubun S, Sawai T

机构信息

Department of Orthopaedic Surgery, Naruko National Hospital, Miyagi.

出版信息

Ryumachi. 1997 Oct;37(5):688-95.

PMID:9396371
Abstract

OBJECTIVE

Rapidly destructive coxarthropathy (RDC) is characterized by rapid destruction of hip joints, but its pathogenetic mechanism is still obscure. Matrix metalloproteinases (MMPs) are possibly one of the candidates concerning with this mechanism. We attempted histochemical investigation to demonstrate MMPs and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues obtained from RDC patients to clarify their roles in the destruction mechanism.

MATERIALS AND METHODS

Joint tissues including synovia and cartilage-bone tissues were obtained from RDC patients at total hip replacement (THR). After fixation with 4% paraformaldehyde, cartilage-bone tissues were partly decalcified. We performed histochemical study for paraffin sections of these tissues by using avidin-biotin method. Antibodies used in this study were monoclonal antibodies to MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2 and polyclonal antibody to MMP-3.

RESULTS

Histological feature of RDC was severe destruction of cartilage and bone by invasion of non-specific granulation tissues composed of many small vessels, macrophages and fibroblastic cells. At the same time, RDC showed apparently fewer lymphocytic cells in these granulation tissues compare with rheumatoid arthritis. MMP-2 and MMP-9 were expressed most demonstrably in synovia and destructive regions of femoral heads, especially in osteoclasts, macrophages, and fibroblastic cells, while MMP-1, MMP-3, were slightly expressed only in the superficial layer of synovia in limited cases. MMP-8, usually contained in neutrophils, was not present in RDC. On the other hand TIMP-1 and TIMP-2 were presented throughout the synovia and destructive regions of femoral heads including fibroblastic cells, macrophages, osteoblasts and osteocytes.

CONCLUSION

Immunohistochemical study revealed obvious presence of MMP-2 and MMP-9 in synovia and destructive regions of femoral heads in RDC. Those evidence suggest that MMP-2 and MMP-9 share very important role in the destructive mechanism of RDC, possibly under imbalance between TIMPs.

摘要

目的

快速破坏性髋关节病(RDC)的特征是髋关节迅速破坏,但其发病机制仍不清楚。基质金属蛋白酶(MMPs)可能是与该机制相关的候选因素之一。我们尝试进行组织化学研究,以证明RDC患者关节组织中的MMPs和金属蛋白酶组织抑制剂(TIMPs),从而阐明它们在破坏机制中的作用。

材料与方法

在全髋关节置换术(THR)时从RDC患者获取包括滑膜和软骨-骨组织的关节组织。用4%多聚甲醛固定后,软骨-骨组织进行部分脱钙。我们使用抗生物素蛋白-生物素方法对这些组织的石蜡切片进行组织化学研究。本研究中使用的抗体是针对MMP-1、MMP-2、MMP-7、MMP-8、MMP-9、TIMP-1、TIMP-2的单克隆抗体以及针对MMP-3的多克隆抗体。

结果

RDC的组织学特征是由许多小血管、巨噬细胞和成纤维细胞组成的非特异性肉芽组织侵入导致软骨和骨的严重破坏。同时,与类风湿性关节炎相比,RDC在这些肉芽组织中的淋巴细胞明显较少。MMP-2和MMP-9在滑膜和股骨头破坏区域表达最明显,尤其是在破骨细胞、巨噬细胞和成纤维细胞中,而MMP-1、MMP-3仅在有限病例的滑膜表层有轻微表达。通常存在于中性粒细胞中的MMP-8在RDC中不存在。另一方面,TIMP-1和TIMP-2存在于整个滑膜和股骨头破坏区域,包括成纤维细胞、巨噬细胞、成骨细胞和骨细胞。

结论

免疫组织化学研究显示RDC患者滑膜和股骨头破坏区域明显存在MMP-2和MMP-9。这些证据表明MMP-2和MMP-9在RDC的破坏机制中起非常重要的作用,可能是在TIMPs失衡的情况下。

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